The following facts were established: (1) Labelled aspartate will appear in the urine as GSA, yet transamidination from arginine or canavanine does not take place to aspartate. (2) GAA concentration is markedly decreased in the urine of the uremic while guanidinosuccinate is markedly increased. (3) Canavanine will transamidinate glycine to form ureido-homoserine. (4) Human kidney catalyzes the condensation of canavanine with fumarate to form CSA. (5) CSA is reduced in the presence of liver and Fe ions, by reduced lipoate to Form GSA, and homoserine. (6) Neomycin ingestion, to sterilize the intestinal tract, does not lower the GSA in the urine of humans in uremia. All of these facts may be made consistent if the urea-cycle enzymes act in the canavanine series as they do for arginine. This proposes a second way of forming CSA, namely from aspartate and ureido-homoserine by the condensing enzyme (L-citrulline: L-aspartate ligase, 6.3.4.5). Degradation of CSA occurs by either of two pathways, cleavage to fumarate and canavanine (lyase pathway), or by reduction to homoserine and GSA. Blockage of th lyase pathway, due to kidney disease, will decrease the canavanine formed and increase the GSA formed. Decrease of canavanine production will then reduce the amount of GAA formed by transamidination. Thus, an inverse ratio exists between GAA and GSA. GSA originates with aspartate through its condensation with ureidohomoserine to form CSA. Studies are under way to compare the rate of creatine formation by transamidination from arginine and the pathway under study.